a b s t r a c tLab-on-a-chip (LOC) devices are broadly used for research in the life sciences and diagnostics and represent a very fast moving field. LOC devices are designed, prototyped and assembled using numerous strategies and materials but some fundamental trends are that these devices typically need to be (1) sealed, (2) supplied with liquids, reagents and samples, and (3) often interconnected with electrical or microelectronic components. In general, closing and connecting to the outside world these miniature labs remain a challenge irrespectively of the type of application pursued. Here, we review methods for sealing and connecting LOC devices using standard approaches as well as recent state-of-the-art methods. This review provides easy-to-understand examples and targets the microtechnology/engineering community as well as researchers in the life sciences.

Point-of-care (POC) immunodiagnostic tests play a crucial role in enabling rapid and correct diagnosis of diseases in prehospital care, emergency, and remote settings. In this work, we present a silicon-based, capillary-driven microfluidic chip integrating two microfluidic modules for the implementation of highly miniaturized immunoassays. Specifically, we apply state-of-the-art microfluidic technology to demonstrate a one-step immunoassay for the detection of the cardiac marker troponin I in human serum using sample volumes of ∼1 μL and with a limit of detection (LOD) of ∼4 ng mL–1 within 25 min. The microfluidic modules discussed here broadly map functionalities found in standard lateral flow assays. We implement a self-coalescence module (SCM) for the controlled reconstitution and delivery of inkjet-spotted and dried detection antibodies (dAbs). This allows for homogeneous dissolution of 1.3 ng of fluorescently labeled dAbs in 416 nL of the sample used for the assay. We also show how to immobilize receptors inside closed microfluidic devices in <30 s using bead lane modules inside which microbeads functionalized with capture antibodies (cAbs) are self-assembled. The resulting bead lane module, with a volume of ∼3 × 10–5 mm3, is positioned across the flow path and holds ∼300 5 μm-diameter microbeads. Altogether, these capillary-driven elements allow for the manipulation of samples and reagents with an unprecedented precision and control, paving the way for the next generation of POC immunodiagnostics.

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The ever-increasing need for portable, easy-to-use, cost-effective, and connected point-of-care diagnostics (POCD) has been one of the main drivers of recent research on lab-on-a-chip (LoC) devices. A majority of these devices use microfluidics to manipulate precisely samples and reagents for bioanalysis. However, filling microfluidic devices with liquid can be prone to failure. For this reason, we have implemented a simple, yet efficient method for monitoring liquid displacement in microfluidic chips using capacitive sensing and a compact (75 mm × 30 mm × 10 mm), low-cost ($60), and battery-powered (10-hour autonomy) device communicating with a smartphone. We demonstrated the concept using a capillary-driven microfluidic chip comprising two equivalent flow paths, each with a total volume of 420 nL. Capacitance measurements from a pair of electrodes patterned longitudinally along the flow paths yielded 17 pL resolution in monitoring liquid displacement at a sampling rate of 1 data/s (~1 nL/min resolution in the flow rate). We characterized the system using human serum, biological buffers, and water, and implemented an algorithm to provide real-time information on flow conditions occurring in a microfluidic chip and interactive guidance to the user.

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